tbuckley/cabot-search huggingface dataset:
Sex and anti-inflammatory treatment affect outcome of melanoma and non-small cell lung cancer patients with rheumatic immune-related adverse events
Authors: Karolina Gente, Leonore Diekmann, Lea Daniello, Julia Will, Manuel Feisst, Victor Olsavszky, Janine Günther, Hanns-Martin Lorenz, M Margarida Souto-Carneiro, Jessica C Hassel, Petros Christopoulos, Jan Leipe
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Rheumatic immune-related adverse events (R-irAEs) occur in 5–15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of anti-inflammatory treatment. Methods In this prospective, multicenter, long-term, observational study, R-irAEs were comprehensively analyzed in patients with malignant melanoma (MM, n=50) and non-small cell lung cancer (NSCLC, n=41) receiving ICI therapy who were enrolled in the study between August 1, 2018, and December 11, 2022. Results After a median follow-up of 33 months, progressive disease or death occurred in 66.0% and 30.0% of MM and 63.4% and 39.0% of patients with NSCLC. Male sex (progression-free survival (PFS): p=0.013, and overall survival (OS): p=0.009), flare of a pre-existing condition (vs de novo R-irAE, PFS: p=0.010) and in trend maximum glucocorticoid (GC) doses &gt;10 mg and particularly ≥1 mg/kg prednisolone equivalent (sex-adjusted PFS: p=0.056, OS: p=0.051) were associated with worse cancer outcomes. Patients receiving disease-modifying antirheumatic drugs (DMARDs) showed significantly longer PFS (n=14, p=0.011) and OS (n=20, p=0.018). Effects of these variables on PFS and/or OS persisted in adjusted Cox regression models. Additionally, GC treatment negatively correlated with the time from diagnosis of malignancy and the latency from ICI start until R-irAE onset (all p&lt;0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities. Conclusion Male sex, flare of pre-existing rheumatologic conditions and extensive GC treatment appeared to be linked with unfavorable cancer outcomes, while DMARD use had a favorable impact. These findings challenge the current dogma of restrictive DMARD use for R-irAE and thus may pave the way to better strategies and randomized controlled trials for the growing number of patients with R-irAE.
CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity
Authors: Ramin Salehi-Rad, Raymond J Lim, Yushen Du, Linh M Tran, Rui Li, Stephanie L Ong, Zi Ling Huang, Camelia Dumitras, Tianhao Zhang, Stacy J Park, William Crosson, Bitta Kahangi, Jensen Abascal, Christopher Seet, Michael Oh, Maryam Shabihkhani, Manash Paul, Kostyantyn Krysan, Aaron E Lisberg, Edward B Garon, Bin Liu, Steven M Dubinett
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. Methods Murine models of NSCLC with distinct driver mutations ( Kras G12D /P53 +/- /Lkb1 -/- (KPL); Kras G12D /P53 +/- (KP); and Kras G12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. Results ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. Conclusions CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.
Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment
Authors: Lara Victoria Donhauser, Julia Veloso de Oliveira, Cordula Schick, Wenzel Manlik, Sabrina Styblova, Sarah Lutzenberger, Michael Aigner, Patrick Philipp, Sebastian Robert, Beate Gandorfer, Dirk Hempel, Louisa Hempel, Dietmar Zehn
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Personalized mRNA vaccines are promising new therapeutic options for patients with cancer. Because mRNA vaccines are not yet approved for first-line therapy, the vaccines are presently applied to individuals that received prior therapies that can have immunocompromising effects. There is a need to address how prior treatments impact mRNA vaccine outcomes. Method Therefore, we analyzed the response to BioNTech/Pfizer’s anti-SARS-CoV-2 mRNA vaccine in 237 oncology outpatients, which cover a broad spectrum of hematologic malignancies and solid tumors and a variety of treatments. Patients were stratified by the time interval between the last treatment and first vaccination and by the presence or absence of florid tumors and IgG titers and T cell responses were analyzed 14 days after the second vaccination. Results Regardless of the last treatment time point, our data indicate that vaccination responses in patients with checkpoint inhibition were comparable to healthy controls. In contrast, patients after chemotherapy or cortisone therapy did not develop an immune response until 6 months after the last systemic therapy and patients after Cht-immune checkpoint inhibitor and tyrosine kinase inhibitor therapy only after 12 months. Conclusion Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.
Biofilm formation on endovascular aneurysm repair (EVAR) grafts—a proof of concept in vitro model
Authors: Torgny Sunnerhagen, Franziska Schwartz, Lars Christophersen, Thomas Bjarnsholt, Klaus Qvortrup, Nikolaj Eldrup, Katja Vogt, Claus Moser
Journal: Clinical Microbiology and Infection (2023)

An endovascular aneurysm repair (EVAR) graft is a catheter-implanted vascular prosthesis and is the preferred treatment for patients with aortic aneurysm. If an EVAR graft becomes the focus of infection, the treatment possibilities are limited because it is technically difficult to remove the graft to obtain source control. This study examines whether Pseudomonas aeruginosa and Staphylococcus aureus form biofilm on EVAR prostheses.EVAR graft sections were exposed to bacteria at 102 or 108 colony forming units (CFU)/mL in lysogeny broth and Krebs-Ringer at 37°C, bacterial biofilm formation was evaluated by scanning electron microscopy and counting CFU on the graft sections after antibiotic exposure at × 10 minimal inhibitory concentration. Bacteria were tested for tolerance to benzylpenicillin, tobramycin, and ciprofloxacin.Bacterial exposure for 15 minutes established biofilms on all prosthesis fragments (6/6 replicates). After 4 hours, bacteria were firmly attached to the EVAR prostheses and resisted washing. After 18-24 hours, the median CFU/g of EVAR graft reached 5.2 × 108 (1.15 × 108-1.1 × 109) for S. aureus and 9.1 × 107 (3.5 × 107-6.25 × 108) for P. aeruginosa. Scanning electron microscopy showed bacterial attachment to the graft pieces. There was a time-dependent development of tolerance with approximately 20 (tobramycin), 560 (benzylpenicillin), and 600 (ciprofloxacin) times more S. aureus surviving antibiotic exposure in 24- compared with 0-hour-old biofilm. Five (tobramycin) and 170 times (ciprofloxacin) more P. aeruginosa survived antibiotic exposure in 24- compared with 0-hour-old biofilms.Our results show that bacteria can rapidly adhere to and subsequently form antibiotic-tolerant biofilms on EVAR graft material in concentrations equivalent to levels seen in transient bacteraemia in vivo. Potentially, the system can be used for identifying optimal treatment combinations for infected EVAR prosthesis.
ATM inhibition augments type I interferon response and antitumor T-cell immunity when combined with radiation therapy in murine tumor models
Authors: Won Jong Jin, Luke M Zangl, Meredith Hyun, Elian Massoud, Kaleb Schroeder, Roxana A Alexandridis, Zachary S Morris
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of interferon genes (STING) activation. We investigated whether combining RT with an ataxia-telangiectasia mutated inhibitor promoted these effects and amplified tumor immunity. Methods Mice-bearing syngeneic flank tumors (MOC2 head and neck squamous cell carcinoma or B78 melanoma) were treated with tumor-directed RT and oral administration of AZD0156. Specific immune cell depletion, type 1 interferon receptor 1 knock-out mice (IFNAR1-KO), and STING-deficient tumor cells were used to investigate tumor-immune crosstalk following RT and AZD0156 treatment. Results Combining RT and AZD0156 reduced tumor growth compared with RT or AZD0156 alone in mice bearing MOC2 or B78 tumors. Low-dose AZD0156 (1–100 nM) alone did not affect tumor cell proliferation but suppressed tumor cell clonogenicity in combination with RT. Low-dose AZD0156 with RT synergistically increased IFN-β, major histocompatibility complex (MHC)-I, and programmed death-ligand 1 (PD-L1) expression in tumor cells. In contrast to wild-type mice, IFNAR1-KO mice showed reduced CD8+T cell tumor infiltration and poor survival following RT+AZD0156 treatment. CD8+T cell depletion reduced antitumor response during RT+AZD0156 treatment. STING-deficient MOC2 (MOC2-STING+/–) or B78 (B78-STING–/–) tumors eliminated the effects of RT+AZD0156 on the expression of IFN-β, MHC-I, and PD-L1, and reduced CD8+T cell infiltration and migration. Additional anti-PD-L1 therapy promoted antitumor response by elevation of tumor-MHC-I and lymphocyte activation. Conclusions Combined radiation and AZD0156 increase STING-dependent antitumor response. Tumor-derived cell-autonomous IFN-β amplification drives both MHC-I and PD-L1 induction at the tumor cell surface, which is required by anti-PD-L1 therapy to promote antitumor immune response following RT and AZD0156 combination therapy.
Re: Dot et al.: Incidence of retinal detachment, macular edema, and ocular hypertension after neodymium:yttrium-aluminum-garnet capsulotomy: a population-based nationwide study-The French YAG 2 Study (Ophthalmology. 2022;130:478–487)
Authors: Bharat Gurnani, Kirandeep Kaur
Journal: Ophthalmology (2023)
Signaling-induced systematic repression of miRNAs uncovers cancer vulnerabilities and targeted therapy sensitivity
Authors: Alexander A. Wurm, Silke Brilloff, Sofia Kolovich, Silvia Schäfer, Elahe Rahimian, Vida Kufrin, Marius Bill, Zunamys I. Carrero, Stephan Drukewitz, Alexander Krüger, Melanie Hüther, Sebastian Uhrig, Sandra Oster, Dana Westphal, Friedegund Meier, Katrin Pfütze, Daniel Hübschmann, Peter Horak, Simon Kreutzfeldt, Daniela Richter, Evelin Schröck, Gustavo Baretton, Christoph Heining, Lino Möhrmann, Stefan Fröhling, Claudia R. Ball, Hanno Glimm
Journal: Cell Reports Medicine (2023)

Targeted therapies are effective in treating cancer, but success depends on identifying cancer vulnerabilities. In our study, we utilize small RNA sequencing to examine the impact of pathway activation on microRNA (miRNA) expression patterns. Interestingly, we discover that miRNAs capable of inhibiting key members of activated pathways are frequently diminished. Building on this observation, we develop an approach that integrates a low-miRNA-expression signature to identify druggable target genes in cancer. We train and validate our approach in colorectal cancer cells and extend it to diverse cancer models using patient-derived in vitro and in vivo systems. Finally, we demonstrate its additional value to support genomic and transcriptomic-based drug prediction strategies in a pan-cancer patient cohort from the National Center for Tumor Diseases (NCT)/German Cancer Consortium (DKTK) Molecularly Aided Stratification for Tumor Eradication (MASTER) precision oncology trial. In conclusion, our strategy can predict cancer vulnerabilities with high sensitivity and accuracy and might be suitable for future therapy recommendations in a variety of cancer subtypes.
An artificial intelligence system for the whole process from diagnosis to treatment suggestion of ischemic retinal diseases
Authors: Xinyu Zhao, Zhenzhe Lin, Shanshan Yu, Jun Xiao, Liqiong Xie, Yue Xu, Ching-Kit Tsui, Kaixuan Cui, Lanqin Zhao, Guoming Zhang, Shaochong Zhang, Yan Lu, Haotian Lin, Xiaoling Liang, Duoru Lin
Journal: Cell Reports Medicine (2023)

Ischemic retinal diseases (IRDs) are a series of common blinding diseases that depend on accurate fundus fluorescein angiography (FFA) image interpretation for diagnosis and treatment. An artificial intelligence system (Ai-Doctor) was developed to interpret FFA images. Ai-Doctor performed well in image phase identification (area under the curve [AUC], 0.991-0.999, range), diabetic retinopathy (DR) and branch retinal vein occlusion (BRVO) diagnosis (AUC, 0.979-0.992), and non-perfusion area segmentation (Dice similarity coefficient [DSC], 89.7%-90.1%) and quantification. The segmentation model was expanded to unencountered IRDs (central RVO and retinal vasculitis), with DSCs of 89.2% and 83.6%, respectively. A clinically applicable ischemia index (CAII) was proposed to evaluate ischemic degree; patients with CAII values exceeding 0.17 in BRVO and 0.08 in DR may be associated with increased possibility for laser therapy. Ai-Doctor is expected to achieve accurate FFA image interpretation for IRDs, potentially reducing the reliance on retinal specialists.
Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial
Authors: Wenwen Zhang, Shuang Tong, Bingyang Hu, Tao Wan, Haowen Tang, Feilong Zhao, Tianyu Jiao, Junfeng Li, Ze Zhang, Jinping Cai, Huiyi Ye, Zhanbo Wang, Shiqing Chen, Yafei Wang, Xuerui Li, Fangzhou Wang, Junning Cao, Lantian Tian, Xiaochen Zhao, Mingyi Chen, Hongguang Wang, Shouwang Cai, Minggen Hu, Yuezong Bai, Shichun Lu
Journal: Journal for ImmunoTherapy of Cancer (2023)

Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease.This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives.Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders.Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen.Chinese Clinical Trial Registry, ChiCTR1900023914.
Learning during sleep in humans – A historical review
Authors: Somayeh Ataei, Eni Simo, Mathijs Bergers, Sarah F. Schoch, Nikolai Axmacher, Martin Dresler
Journal: Sleep Medicine Reviews (2023)

Sleep helps to consolidate previously acquired memories. Whether new information such as languages and other useful skills can also be learned during sleep has been debated for over a century, however, the sporadic studies' different objectives and varied methodologies make it difficult to draw definitive conclusions. This review provides a comprehensive overview of the history of sleep learning research conducted in humans, from its empirical beginnings in the 1940s to the present day. Synthesizing the findings from 51 research papers, we show that several studies support the notion that simpler forms of learning, such as habituation and conditioning, are possible during sleep. In contrast, the findings for more complex, applied learning (e.g., learning a new language during sleep) are more divergent. While there is often an indication of processing and learning during sleep when looking at neural markers, behavioral evidence for the transfer of new knowledge to wake remains inconclusive. We close by critically examining the limitations and assumptions that have contributed to the discrepancies in the literature and highlight promising new directions in the field.
A SARS-CoV-2 and influenza rapid antigen test-based hospital isolation policy awaiting RT-PCR, a prospective observational study
Authors: Nathalie Van der Moeren, Vivian F Zwart, Marie Louise van Leest, Marcel Thijssen, Robbert Groenewegen, Marieke Kuipers-de Heer, Jean-Luc Murk, Jeroen T Tjhie, Bram M W Diederen, Joep J J M Stohr
Journal: Clinical Microbiology and Infection (2023)
Physiopathology and clinical management of blackwater fever: a scoping review
Authors: Paola Rodari, Francesca Tamarozzi, Veronica A. Fittipaldo, Dora Buonfrate, Federico Gobbi
Journal: Clinical Microbiology and Infection (2023)

Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and haemoglobinuria. BWF is a neglected condition and management recommendations are unavailable.
A deep weakly semi-supervised framework for endoscopic lesion segmentation
Authors: Yuxuan Shi, Hong Wang, Haoqin Ji, Haozhe Liu, Yuexiang Li, Nanjun He, Dong Wei, Yawen Huang, Qi Dai, Jianrong Wu, Xinrong Chen, Yefeng Zheng, Hongmeng Yu
Journal: Medical Image Analysis (2023)
Malaria parasite prevalence among migrants: a systematic review and meta-analysis
Authors: Ana Requena-Méndez, Paolo Cattaneo, Rebecca T. Bogale, Helena Marti-Soler, Andreas Wångdahl, Dora Buonfrate, Zeno Bisoffi, Anna Färnert, Azucena Rodríguez-Cuadrado, Begoña Monge-Maillo, Cristina Bocanegra, Fernando Salvador, Ines Oliveira, Joaquin Salas-Coronas, Maria Dolores Corbacho-Loarte
Journal: Clinical Microbiology and Infection (2023)

Asymptomatic malaria infections are highly prevalent in endemic areas.This systematic review aimed to estimate the pooled prevalence of malaria parasites in migrants screened in non-endemic areas.MEDLINE-Ovid, EMBASE, Web of Science, Global Health, Lilacs, Cochrane, and MedRxiv.Cross-sectional studies and observational prospective or retrospective cohort studies conducted in Europe, USA, Canada, Australia, or New Zealand regardless of language or publication status. Studies should include prevalence data on malaria in migrants that were recruited through a systematic screening approach. We excluded studies where people were tested because of malaria symptoms.Migrant individuals exposed to malaria infection ASSESSMENT OF RISK OF BIAS: A standardized and validated appraisal instrument was used for studies reporting prevalence data (Joanna Briggs Institute Manual for Evidence Synthesis).Pooled estimates of the parasite prevalence by PCR, microscopy, and rapid diagnostic test (RDT) were calculated with a random-effects model. Heterogeneity was explored by stratification by age, region of origin, period of study, and quality of studies.Of 1819 studies retrieved, 23 studies were included with in total 4203 participant PCR data, 3186 microscopy and 4698 RDT data, respectively. Migrants from sub-Saharan Africa had a malaria parasite prevalence of 8.3% (95% CI 5.1-12.2) by PCR, 4.3% (1.5-8.2) by RDT, and 3.1% (0.7-6.8) by microscopy. For migrants from Asia and Latin America, the prevalence with PCR was 0% (0.0-0.08) and 0.4% (0.0-1.8), respectively. Migrants from the Central African Region had the highest PCR prevalence (9.3% [6.0-13.0]), followed by West African migrants (2.0% [0.0-7.7]). Restricting the analysis to sub-Saharan Africa migrants arriving to the host country within the previous year, the PCR-based prevalence was 11.6% (6.9-17.4).We provide estimates on the malaria parasite prevalence in migrants in non-endemic setting. Despite heterogeneity between settings, these findings can contribute to inform screening strategies and guidelines targeting malaria in migrants.